The invention relates to a substation high-voltage chamber fully-closed operation system and a control method. The system comprises a high-voltage chamber; the high-voltage chamber is a fully-closed structure; an electric blind window electrically controlled to open and close is mounted in a ventilation port of the high-voltage chamber; an environment active operation maintenance system is mountedin the high-voltage chamber, and comprises an environment monitoring device, a data processing module and an environment auxiliary device; the environment monitoring device collects high-voltage chamber internal environment information and sends to the data processing module; and the data processing module adjusts the environment in the high-voltage chamber through controlling the environment auxiliary device. Through intelligent control of the temperature and the humidity, the operation environment is optimized, the electric insulation intensity of switch cabinet equipment is improved, the bus and transformer damage risk caused by failures of the switch cabinet is reduced, the substation safety operation level is improved, and the safety benefit is prominent. The system can be applied tothe high-voltage chamber to eliminate the insulation reduction problem caused by damping and pollution of switch cabinet insulation pieces of small cabinet bodies.